EAACI/GA2LEN Guideline: Aspirin provocation tests for diagnosis of aspirin hypersensitivity. Allergy

Jagiellonian University, Cracovia, Lesser Poland Voivodeship, Poland
Allergy (Impact Factor: 6.03). 11/2007; 62(10):1111-8. DOI: 10.1111/j.1398-9995.2007.01409.x
Source: PubMed


Aspirin and other nonsteroidal anti-inflammatory drugs (NSAIDs) are among the most common causes of adverse drug reactions. Majority of them are of the hypersensitivity type. The two frequent clinical presentations of aspirin hypersensitivity are: aspirin-induced bronchial asthma/rhinosinusitis (AIA/R) and aspirin-induced urticaria/angioedema (AIU). The decisive diagnosis is based on provocation tests with aspirin, as the in vitro test does not hold diagnostic value as yet. Detailed protocols of oral, bronchial and nasal aspirin provocation tests are presented. Indications, contraindications for the tests, the rules of drug withdrawal and equipment are reviewed. Patient supervision and interpretations of the tests are proposed.

Download full-text


Available from: Stefan Wöhrl, Sep 24, 2014
    • "Those AERD patients having a decrease of 20% or more of the baseline FEV 1 but a drop in PNIF values exceeding 40% were considered to manifest both bronchial and nasal reactions (BNR). The degree of airway responsiveness to the oral aspirin challenge was evaluated using the provocative dose causing a 20% or more fall in baseline FEV 1 (PD 20 ASA) calculated according to the EAACI/GA 2 LEN guidelines [18]. Briefly, the lowest FEV 1 value from three measurements (at 30, 60 and 120 min) performed after each administrated dose of aspirin was plotted against the log 10 of the cumulative dose to build a dose–response curve. "
    [Show abstract] [Hide abstract]
    ABSTRACT: Background: Systemic reactions are related to the pathogenesis of Aspirin Exacerbated Respiratory Disease (AERD). With this work we wanted to study the changes in the systemic levels of inflammatory mediators in both baseline and after oral aspirin challenge in patients with and without AERD. Methods: Patients with nasal polyposis and asthma with AERD (n=20) and without (n=18) were orally challenged with aspirin in a single-blind placebo controlled study. Serum samples and urine were collected before and 6h after placebo and aspirin oral challenges. Serum levels of inflammatory mediators were assayed by using the Luminex technology and ELISA. The concentrations of 9-alpha, 11-beta prostaglandin F2, and leukotriene E4 (uLTE4) were measured in urine samples by ELISA. The expression of T-cell surface markers was analyzed in peripheral blood mononuclear cells isolated before and after the challenges. Results: AERD patients showed significantly higher baseline levels of s-IL-5R-alpha, uLTE4 and percentage of CD4(+)CD25(+)CD127(pos) and CD4(+)CD45RA(-)CD45RO(+) but decreased levels of TGF-β1 and number of CD4(+)CD25(+)CD127(neg) cells. Aspirin challenge induced the release of uLTE4, IL-6 and increased the number of CD4(+)CD45RA(-)CD45RO(+) memory T-cells only in AERD patients but failed to reduce the levels of sCD40L as observed in non-AERD subjects. Further, IL-8 and sIL-5R-alpha levels directly correlated with the PD20ASA and the effects of aspirin on IL-6 and number of memory T-cells was more pronounced in subjects showing more strong reaction (bronchial and nasal). Conclusions: AERD patients have a differential baseline inflammatory pattern that supports the role inflammation as underlying mechanism of the disease. Systemic response to oral aspirin challenge was related to an increase in serum IL-6 and the number of circulating memory T-cells in AERD patients.
    No preview · Article · Jan 2016 · Cytokine
  • Source
    • "However, to minimize the effect of the open provocation method, we regarded the provocation test as positive when only objective changes in signs were detected. Second, the time interval between each challenge dose in the common protocol we used in our clinic was shorter than that recommended by a consensus report.14 No analysis of the exact provocative dose was available. "
    [Show abstract] [Hide abstract]
    ABSTRACT: Identification of tolerable alternative analgesics is crucial for management in nonsteroidal anti-inflammatory drug (NSAID)-sensitive patients. We investigated cross-reactivity of acetaminophen and celecoxib according to the type of aspirin/NSAID hypersensitivity and aimed to determine the risk factors for cross-intolerance. We retrospectively reviewed the medical records of patients intolerant to aspirin and NSAIDs who had undergone an acetaminophen and/or celecoxib oral provocation test. Aspirin/NSAID hypersensitivity was classified into 4 types according to a recently proposed classification: aspirin-exacerbated respiratory disease (AERD), aspirin-exacerbated chronic urticaria (AECU), aspirin-induced acute urticaria/angioedema (AIAU), and NSAID-induced blended reaction (NIRD). A total of 180 patients with hypersensitivity to aspirin and NSAIDs were enrolled; 149 acetaminophen provocation test results and 145 celecoxib provocation test results were analyzed. The overall cross-reaction rates to acetaminophen and celecoxib were 24.8% and 10.3%, respectively. There was a significant difference in the cross-reactivity to acetaminophen according to the type of NSAID hypersensitivity. Cross-reactivity to acetaminophen was highest in the AECU group (43.9%), followed by the AERD (33.3%), NIBR (16.7%), and AIAU (12.5%) groups. Underlying chronic urticaria was more prevalent in patients with cross-intolerance to both acetaminophen (P=0.001) and celecoxib (P=0.033). Intolerance to acetaminophen was associated with intolerance to celecoxib (P<0.001). Acetaminophen and celecoxib may induce adverse reactions in a non-negligible portion of aspirin/NSAID-sensitive patients. Physicians should be aware of the possible cross-reactions of these alternative drugs and consider an oral challenge test to confirm their tolerability.
    Full-text · Article · Mar 2014 · Allergy, asthma & immunology research
  • Source
    • "Therapeutic options to diagnose NSAID hypersensitivity are still limited. Oral drug challenge (preferably placebo controlled) is the gold standard in diagnosing NSAID hypersensitivity [12,13]. "
    [Show abstract] [Hide abstract]
    ABSTRACT: Non-steroidal anti-inflammatory drugs (NSAIDs) frequently cause adverse drug reactions. Many studies have shown that drugs which selectively inhibit the cyclooxygenase-2 enzyme (COX-2) are safe alternatives in the majority of patients. However, hypersensitivity reactions to COX-2 inhibitors have been published. Hardly any data are available regarding the safety of alternatives in case of COX-2 inhibitor hypersensitivity. We aimed to investigate the tolerance to COX-2 inhibitors in patients with non-selective NSAID hypersensitivity. Furthermore, in COX-2 hypersensitive patients tolerance of a second COX-2 inhibitor was investigated. We retrospectively analyzed 91 patients with proven non-selective NSAID hypersensitivity that underwent oral challenges with a COX-2 inhibitor. Patients with intolerance to the first challenged COX-2 inhibitor received a second challenge with a different COX-2 inhibitor. 19 out of 91 (21% ) patients had a positive reaction to the first oral challenge with a COX-2 inhibitor. 14 of them underwent a second challenge with a different COX-2 inhibitor and 12 (86% ) did not react. A relatively high percentage (21% ) of the non-selective NSAID hypersensitive patients did not tolerate a COX-2 inhibitor and oral challenge is advised prior to prescription of a COX-2 inhibitor. For the majority of patients reacting to a COX-2 inhibitor an alternative can be found.
    Full-text · Article · Jun 2013
Show more